Potassium channels are ubiquitous in eukaryote and prokaryote cells. Their exceptional functional diversity make them ideal candidates for a large number of biological processes in living cells (Rudy, B., 1988, Neurosciences, 25, 729-749; Hille, B., 1992, "Ionic Channels of Excitable Membrane", 2nd edition, Sinauer, Sunderland, Mass.). In excitable cells, the K.sup.+ channels define the form of the action potentials and the frequency of the electric activity, and play a major role in neuronal integration, muscle contraction or hormonal secretion. In nonexcitable cells, their expression appears to be correlated with specific stages of the development of the cell (Barres, B. A. et al., 1990, Annu. Rev. Neurosci., 13, 441-474). In most cells, specific types of K.sup.+ channels play a vital role in determining the electrical potential of the membrane at rest by regulating the membrane permeability to K.sup.+ ions. These channels exhibit the characteristic of being instantaneous and open in a large range of membrane potentials.
Recent cloning studies have resulted in the identification of a large number of subunits capable of forming potassium channels (Betz, H., 1990, Biochemistry, 29, 3591-3599; Pongs, O., 1992, Physiol. Rev., 72, S69-88; Salkoff, L. et al., 1992, Trends Neurosci., 15, 161-166; Jan, L. Y. and Y. N. Jan, 1994, Nature, 371, 199-122; Doupnik, C. A. et al., 1995, Curr. Opin. Neurobiol., 5, 268-277) which could be regulated by other types of subunits (Aldrich, R. W., 1994, Curr. Biol., 4, 839-840; Isom, L. L. et al., 1994, Neuron, 12, 1183-1194; Rettig, J. et al., 1994, Nature, 369, 289-294; Attali, B. et al., 1995, Proc. Natl. Acad. Sci. USA, 92, 6092-6096).
The subunits of the voltage-dependent K.sup.+ channels activated by depolarization (Kv families) and the calcium-dependent K.sup.+ channels exhibit six hydrophobic transmembranal domains, one of which (S4) contains repeated positive charges which confer on these channels their sensitivity to voltage and, consequently, in their functional outward rectification (Logothetis, D. E. et al., 1992, Neuron, 8, 531-540; Bezanilla, F. and Stefani, E., 1994, Annu. Rev. Biophys. Biomol. Struct., 23, 819-846).
The K.sup.+ channels with inward rectification (Kir families) have only two transmembranal domains. They do not have the S4 segment and the inward rectification results from a voltage-dependent blockade by cytoplasmic magnesium (Matsuda, H., 1991, Annu. Rev. Physiol., 53, 289-298; Lu, Z. and Mackinnon, R., 1994, Nature, 371, 243-246; Nichols, C. G. et al., 1994, J. Physiol. London, 476, 399-409).
A common structural unit, called the P domain, is found in both groups, and constitutes an essential element of the structure of the K.sup.+ -permeable pore. The presence of this unit in a membrane protein is considered to be the signature of the structure of a K.sup.+ channel (Pongs, O., 1993, J. Membrane Biol., 136, 1-8; Heginbotham, L. et al., 1994, Biophys. J., 66, 1061-1067; Mackinnon, R., 1995, Neuron, 14, 889-892; Pascual, J. M. et al., 1995, Neuron, 14, 1055-1063).